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Plasmacytoid Dendritic Cell Precursors Induce Allogeneic T‐Cell Hyporesponsiveness and Prolong Heart Graft Survival
Author(s) -
Abe Masanori,
Wang Zhiliang,
De Creus An,
Thomson Angus W.
Publication year - 2005
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2005.00954.x
Subject(s) - dendritic cell , cd11c , t cell , immunology , medicine , population , cd19 , microbiology and biotechnology , immune system , biology , phenotype , biochemistry , environmental health , gene
Dendritic cell (DC) precursors were propagated from C57BL/10 (B10; H2 b ) mouse bone marrow in fms‐like tyrosine kinase 3 ligand. Cosignaling molecule (B7‐1/B7‐2 and B7‐H1) expression and stimulatory capacity of precursor (pre)‐plasmacytoid (p)DC (CD11c + B220 + CD11b − CD19 − ) and classic myeloid DC (MDC) for allogeneic (C3H; H2 k ) T cells were compared. Unstimulated pre‐pDC exhibited very low levels of surface MHC class II and classic costimulatory molecules (B7‐1/B7‐2), whereas a minor population expressed B7‐H1 at levels higher than on MDC. The pre‐pDC were ineffective T‐cell stimulators and induced nonspecific hyporesponsiveness to rechallenge with donor alloantigens in vitro and in vivo . Following stimulation with CpG‐oligonucleotide (CpG‐ODN), B7 molecule expression was upregulated on pre‐pDC, however the ratio between coinhibitory (B7‐H1) and costimulatory (B7‐1/B7‐2) signals was much higher (five‐ to six‐fold) on pre‐pDC than MDC. Blockade of B7‐H1 expression on pDC increased their T‐cell allostimulatory capacity significantly. A single preoperative infusion of C3H hosts with pre‐pDC prolonged B10 heart graft survival significantly but nonspecifically compared with untreated mice (median survival times 22 vs. 9 days, respectively). Thus, pre‐pDC of donor origin have potential to regulate T‐cell responses to alloantigens and can prolong organ graft survival.